Vol. 285, Issue 2, 643-650, May 1998

5-Hydroxytryptamine₂ Receptors Modulate Auditory Filtering in the Rat¹

Robert G. Johnson, Karen E. Stevens and Gregory M. Rose

Departments of Pharmacology (R.G.J., G.M.R.) and Psychiatry (K.E.S.), University of Colorado Health Sciences Center, Denver, Colorado

Sensory processing deficits are a hallmark of schizophrenia and can be demonstrated by recording auditory evoked potentials (AEPs) elicited in response to closely paired click stimuli. In nonschizophrenic humans, as well as in rats, the amplitude of the response to the second click is reduced (filtered) compared with the first. In contrast, schizophrenics, or rats treated with amphetamine, generate AEPs that have smaller amplitudes and show little or no reduction in the response to the second click. We sought to evaluate the role of 5-hydroxytryptamine₂ 5-HT₂ receptors in auditory filtering. Male Sprague-Dawley rats were implanted with a skull screw electrode to permit chronic recording of AEPs from a point approximating human vertex. During subsequent recording sessions, pairs of clicks (a conditioning click followed by a test click) were presented 500 msec apart. Parameters of N40, a dominant midlatency component of the AEP, were examined to evaluate the effects of a 5-HT₂ receptor agonist, (±)-2,5-dimethoxy-4-iodoamphetamine (DOI), and a 5-HT₂ receptor antagonist, ketanserin. Systemic administration of ketanserin reduced sensory filtering in a dose-dependent manner. Conversely, DOI significantly improved filtering. In addition, DOI dose-dependently antagonized the disruption of filtering induced by administration of amphetamine (1.83 mg/kg i.p.). Taken together, these results indicate an important role for 5-HT₂ receptors in the modulation of auditory filtering.